Type 1 Diabetes

Though sometimes called juvenile-onset diabetes or insulin dependent diabetes mellitus (IDDM), type 1 diabetes can affect people of any age and accounts for between 5-10% of all cases³. While the aetiology of this disease is not fully understood, it is known that cellular-mediated autoimmune destruction of the insulin producing β-cells of the pancreas occurs, and people with this form of diabetes need regular injections of insulin to control the levels of glucose in their blood.

Type 2 Diabetes

Sometimes referred to as non-insulin-dependent diabetes or adult-onset diabetes and accounts for between 90-95% of cases, type 2 diabetes is characterised by individuals who are resistant to insulin and usually have relative rather than absolute deficiency. It is thought that there could be many different causes of this form of diabetes but destruction of the β-cells of the pancreas does not occur. The diagnosis of this disease usually occurs after the age of 40 but can occur earlier, especially in populations with high prevalence of diabetes. It is frequently (though not always) associated with obesity.

Gestational Diabetes (GDM)

Gestational diabetes occurs in approximately 1 in 25 pregnancies worldwide when women who have no history of diabetes, develop high blood glucose during pregnancy. It is associated with complications in the period immediately before and after the birth but women with GDM, and their offspring are at an increased risk of developing type 2 diabetes later in life².

Symptoms of Diabetes

Type 1 diabetes tends to develop suddenly and quickly and symptoms include:

• Frequent urination
• Excess thirst
• Blurred Vision
• Weight loss
• Extreme hunger
• Fatigue
• Frequent infections
• Slow-healing wounds

Because type 2 diabetes develops slowly, people may remain unaware of their condition for some time as the classic symptoms may take years to develop or be recognised and many people only being diagnosed when the complications of the illness become evident. There are several risk factors associated with type 2 diabetes which include

• Obesity
• Poor diet
• Age
• Family history
• Ethnicity
• Low activity levels

Diagnosis and Monitoring of Diabetes

Fasting Plasma Glucose and Oral Glucose Tolerance Test

Diabetes, being characterised by recurrent or persistent hyperglycaemia is diagnosed by measuring blood sugar. The diagnostic cut-off point for diabetes is a fasting plasma glucose (FPG) level greater than 7.0 mmol/L (126mg/dL) or a 2 hour oral glucose tolerance test (OGTT ) level greater than 11.1 mmol/L (200mg/dL). This decision was made on the basis that retinopathy increased linearly above these levels.

In 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus5 recommended FPG as the more reproducible and easier to perform test but nonetheless a study by Ollerton⁶ cited by the National Academy of Clinical Biochemistry⁷  suggests that using a theoretically perfect measurement for glucose, a patient with an average FPG of 126mg/dL could have reported concentrations ranging from 109mg/dL to 143mg/dL in 19 of the 20 days and higher or lower than this on the 20th day. This variation would be more pronounced if the samples were obtained at different times of the day as FPG is higher in the morning than the afternoon^8,9.

A third method of assessing glycaemic control of diabetes is the use of glycated serum proteins such as fructosamine to identify plasma glucose concentrations over time. Again, there is no standard reference range available for this test and results can be highly variable from day to day.

Glycated Haemoglobin (HbA1c)

Glycated haemoglobin has a particular clinical interest in diabetes mellitus. Measurement of HbA1c is a clinically useful means of diagnosing diabetes and subsequently assessing glycaemic control in diabetics. Glycated haemoglobin values reflect blood glucose levels over the circulatory half-life of the erythrocyte and correlate significantly with mean blood glucose levels during that time. Therefore, HbA1c measurement of provides a means, independent of multiple measurements such as patient records of self-monitored blood glucose, for assessing the overall efficacy of therapy.

In the past, glycated haemoglobin assays were considered too variable and lacking in standardisation to be considered as a diagnostic assay for diabetes, however due to the Diabetes Control and Complications Trial (DCCT)¹⁰, a major clinical study conducted from 1983 to 1993 funded by the National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK), and the National Glycohemoglobin Standardization Program (NGSP), this is no longer the case. The DCCT trial showed that keeping bloody sugar levels as close to normal as possible slows the onset and progression of diseases caused by diabetes, for example:

• Retinopathy - 76% reduced risk 
• Kidney damage - 50% reduced risk
• Nerve damage - 60% reduced risk

In 2009, the International Expert Committee reviewed the evidence, existing and emerging, and recommended that HbA1c be used to diagnose diabetes, with 6.5% A1c being the cut-off point. This, like the FPG and OGTT cut-offs, is the inflection point for retinopathy prevalence.^11,12

References

1. IDF Diabetes Atlas, 5th Edition, 2011
2. www.idf.org
3. American Diabetes Association. Diagnosis and classification of diabetes mellitus.  Diabetes Care, 2010;33: Supplement 1.
4. Harris Ml, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 years before clinical diagnosis. Diabetes Care, 1992;15:815-9
5. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care.1997; 20: 1183-97.
6. Ollerton RL, Playle R, Ahmed K, Dunstan FD, Luzio SD, Owens DR. Day-to-day variability of fasting plasma glucose in newly diagnosed type 2 diabetic subjects. Diabetes Care. 1999;22:394-398.
7. Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2002;48:436-472.
8. Troisi RJ, Cowie CC, Harris MI. Diurnal variation in fasting plasma glucose: Implications for diagnosis of diabetes in patients examined in the afternoon. JAMA. 2000;284:3157-3159.
9. www.cap.org
10. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal of Medicine. 1993; 329:977-986
11. International Expert Committee. International Expert Committee report on the rold of the A1c assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327-34.
12. Kirkman MS, Kendall DM. Hemoglobin A1c to diagnose diabetes. Why the controversy over adding a new tool? Clin Chem. 2011; 57:2 255-257.